Occupational Exposure to Pesticides Affects Pivotal Immunologic Anti-Tumor Responses in Breast Cancer Women from the Intermediate Risk of Recurrence and Death

• Published in: Cancers Vol. 14; no. 21; p. 5199
• Main Authors: da Silva, Janaína Carla, Scandolara, Thalita Basso, Kern, Rodrigo, Jaques, Hellen dos Santos, Malanowski, Jessica, Alves, Fernanda Mara, Rech, Daniel, Silveira, Guilherme Ferreira, Panis, Carolina
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 23-10-2022; MDPI
• Subjects: Antigens; Biology; Body weight; Breast cancer; Cancer; CD4 antigen; CD8 antigen; Clinical outcomes; CTLA-4 protein; Cytokines; Cytotoxicity; Death; Enzymes; Growth factors; Health aspects; Inflammation; Interleukin 12; Interleukin 4; Lymph nodes; Lymphocytes; Medical prognosis; Metastases; Nitric oxide; Occupational exposure; Occupational health and safety; Oncology, Experimental; Oxidative stress; Patients; Pesticides; Plasma; Relapse; Risk assessment; Risk factors; Software; Toxicity; Transforming growth factor-b1; Tumor cells; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Womens health; Brazil; United States > US
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14215199

Breast cancer risk stratification is a strategy based using on clinical parameters to predict patients’ risk of recurrence or death, categorized as low, intermediate, or high risk. Both low and high risk are based on well-defined clinical parameters. However, the intermediate risk depends on more malleable parameters. It means an increased possibility for either suboptimal treatment, leading to disease recurrence, or systemic damage due to drug overload toxicity. Therefore, identifying new factors that help to characterize better the intermediate-risk stratification, such as environmental exposures, is necessary. For this purpose, we evaluated the impact of occupational exposure to pesticides on the systemic profile of cytokines (IL-12, IL-4, IL-17A, and TNF-α) and oxidative stress (hydroperoxides, total antioxidants, and nitric oxide metabolites), as well as TGF-β1, CTLA-4, CD8, and CD4 expression, investigated in tumor cells. Occupational exposure to pesticides decreased the levels of IL-12 and significantly increased the expression of TGF-β1 and CTLA-4 in the immune infiltrate. Nevertheless, we observed a decrease in CTLA-4 in tumor samples and CD8 in infiltrating cells of intermediate overweight or obese patients with at least one metastatic lymph node at the diagnosis. These findings indicate that occupational exposure to pesticides changes the molecular behavior of disease and should be considered for intermediate-risk stratification assessment in breast cancer patients.